Nucleophilic Substitution Reactions of Thiophenyl Cyclobutanecarboxylates with Benzylamines in Acetonitrile

Abstract

The aminolyses of acyl compounds have been studied extensively. Bronsted plots were used in these reactions as mechanistic criteria. In many of these nucleophilic reactions curved Bronsted type plots have been found, which have been attributed to a change in the rate-determing step from breakdown (βnuc ≅ 0.8-1.0) to formation (βnuc ≅ 0.1-0.3) of a tetrahedral intermediate, T, in the reaction path as a basicity of the amine nucleophile increases. The aminolysis of thiophenyl benzoates with benzylamines, however, exhibited an unusually large βX (βnuc = 1.86) in acetonitrile, which was considered to proceed through a rate-limiting breakdown of a tetrahedral zwitterionic intermediate, T. Benzylamines are primary amines with relatively high basicities (pKa ≥9.0) due to localized cationic charge on the benzylammonium ion and their nucleofugality from T may be much different from that of the secondary and tertiary amines, especially from a sulfur zwitterionic tetrahedral intermediate since it is known that ArS− is a poorer leaving group from T than an isobasic ArO− group. In this paper, we extend our work to the aminolysis of thiophenyl cyclobutanecarboxylates (TCC) with benzylamines (BA) in acetonitrile (eqn. 1).